This study is being conducted to explore the immunological mechanism of action of Peptide-coated Conditionally Replicating Adenovirus-1 (PeptiCRAd-1) plus Checkpoint inhibitor (CPI) therapy in multiple cancer types, as well as to obtain early information on the safety of this combination therapy.
Written informed consent.
Male or female, ≥18 years of age.
Inoperable/metastatic cutaneous malignant melanoma
Relapsed or newly diagnosed locally advanced inoperable/metastatic TNBC
Receipt of any oncolytic virus treatment, or administration of a vaccine containing live virus within 4 weeks before Day 1.
Use of significant immunosuppressive medication, including high dose corticosteroid (defined as the equivalent of >10 mg/day prednisone) within 4 weeks before Day 1. Inhaled or topical corticosteroid use is allowed.
Prior or concomitant radiotherapy within 4 weeks before Day 1.
Participation in a study with an investigational drug or device within 4 weeks prior to Day 1.
Sequential
PeptiCRAd-1
DrugAll patients will receive PeptiCRAd-1.
Cyclophosphamide
DrugAll patients will be pre-treated with one single dose of Cyclophosphamide.
Pembrolizumab
DrugAll patients will receive 6 doses of Pembrolizumab within the study.
Measurement of Safety and tolerability indexes (Incidence of TEAEs, SAEs and DLTs as assessed by CTCAE version 5.0 and changes in assessed safety parameters) for PeptiCRAd-1 monotherapy.
The incidence and characteristics of treatment-emergent adverse events (TEAEs), serious adverse events (SAEs) and dose-limiting toxicities (DLTs) will be assessed by CTCAE version 5.0 and changes from baseline in assessed safety parameters (Hematology tests, Clinical Chemistry safety tests, urine analysis ECOG/WHO performance status, vital signs) are measured in patients receiving PeptiCRAd-1 monotherapy in order to evaluate the safety and tolerability.
Measurement of Safety and tolerability indexes (Incidence of TEAEs, SAEs and DLTs as assessed by CTCAE version 5.0 and changes in assessed safety parameters) for PeptiCRAd-1 and CPI combination.
The incidence and characteristics of TEAEs, SAEs and DLTs will be assessed by CTCAE version 5.0 and changes from baseline in assessed safety parameters (Hematology tests, Clinical Chemistry safety tests, urine analysis ECOG/WHO performance status, vital signs) are measured in patients receiving PeptiCRAd-1 and CPI combination in order to evaluate the safety and tolerability.
Measurement of New York Esophageal Squamous Cell Carcinoma-1 (NY-ESO-1) and Melanoma-associated antigen 3 (MAGE A3) specific T-cells in peripheral blood.
Presence vs. no presence of cellular immune response.
Measurement of NY-ESO-1 and MAGE A3 antibodies in serum.
Presence vs. no presence of humoral response.
To determine the number of tumor infiltrating lymphocytes (TILs) in tumor mass.
Number of TILs in tumor biopsies.
To determine objective response rate (ORR).
Objective responses according to RECIST 1.1, iRECIST, itRECIST and PERCIST 1.0.
Measurement of PFS according to RECIST 1.1, itRECIST, and PERCIST 1.0.
Progression free survival (PFS) is measured, according to RECIST 1.1, iRECIST, itRECIST, and PERCIST 1.0, and will be presented using the Kaplan-Meier approach.
Measurement of virus shedding profiles (presence of infective virus and virus DNA in blood, urine, buccal, fecal and injection site swabs by infectivity assay and qPCR).
Presence of infective virus (infectivity assay) and virus DNA (quantitative polymerase chain reaction, qPCR) will be measured in blood, urine, buccal, fecal and injection site swabs.
Immune phenotyping in tumor mass.
Measurement of biological and immunological changes (including number of T-cells) in biopsies of injected and non-injected tumors over time.
Measurement of the phenotype of circulating immune cells in peripheral blood.
The immunological landscape in peripheral blood will be determined.
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